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Pesticides in the Diets of Infants and Children PESTICIDES in the DIETS OF INFANTS AND CHILDREN Committee on Pesticides in the Diets of Infants and Children Board on Agriculture and Board on Environmental Studies and Toxicology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1993
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Pesticides in the Diets of Infants and Children NATIONAL ACADEMY PRESS 2101 Constitution Avenue Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. Support for this project was provided by the U.S. Environmental Protection Agency, Contract No. 68D-80101, with contributions from International Life Sciences Institute and Health and Welfare Canada. In addition, support for this project was provided by the Kellogg Endowment Fund of the National Academy of Sciences and the Institute of Medicine. Library of Congress Cataloging-in-Publication Data National Research Council (U.S.). Committee on Pesticides in the Diets of Infants and Children. Pesticides in the diets of infants and children/Committee on Pesticides in the Diets of Infants and Children, Board on Agriculture and Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council. p. cm. Includes bibliographical references and index. ISBN 0-309-04875-3 1. Pediatric toxicology. 2. Pesticide residues in food—United States. 3. Pesticides—Toxicology. 4. Infant formulas—Contamination. 5. Food contamination. I. Title. [DNLM: 1. Pesticides. 2. Diet—in infancy & childhood. 3. Food Contamination. WS 115 N277p 1993] RA1225.N38 1993 615.9'54—dc20 DNLM/DLC for Library of Congress Copyright 1993 by the National Academy of Sciences. All rights reserved. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project. Additional copies of this book are available from the National Academy Press, 2101 Constitution Avenue, NW, Box 285, Washington, DC 20055. Call 800-624-6242 or 202-334-3313 (in the Washington Metropolitan Area). Printed in the United States of America First Printing, June 1993 Second Printing, August 1993 Third Printing, November 1993 Fourth Printing, September 1997
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Pesticides in the Diets of Infants and Children COMMITTEE ON PESTICIDES IN THE DIETS OF INFANTS AND CHILDREN PHILIP J. LANDRIGAN, Chair, Mount Sinai School of Medicine, New York DONALD R. MATTISON, Vice-Chair, Graduate School of Public Health, University of Pittsburgh, Pittsburgh HARVEY J. BABICH, Rockefeller University and Yeshiva University, New York BARBARA BOARDMAN, Boston University Medical School and Boston City Hospital Pediatrics, Boston JAMES V. BRUCKNER, University of Georgia, Athens MICHAEL A. GALLO, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway DONALD E. HUTCHINGS, New York State Psychiatric Institute, New York RICHARD J. JACKSON, California State Department of Health Services, Berkeley MERYL H. KAROL, Graduate School of Public Health, University of Pittsburgh, Pittsburg DANIEL KREWSKI, Health and Welfare Canada, Ottawa, Ontario GEORGE A. PURVIS, Gerber Products Company, Fremont, Mich. ROBERT L. RIZEK, U.S. Department of Agriculture, Hyattsville, Md. JAMES N. SEIBER, University of Nevada, Reno WILLIAM B. WEIL, Michigan State University, East Lansing Staff FRANCES M. PETER, Project Manager RICHARD D. THOMAS, Principal Staff Scientist (BEST) CRAIG A. COX, Senior Staff Officer (BA) SANDRA S. FITZPATRICK, Senior Program Assistant (BEST) SHELLEY A. NURSE, Senior Project Assistant (BEST) RUTH P. DANOFF, Project Assistant (BEST)
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Pesticides in the Diets of Infants and Children Technical Advisers EMMANUEL AKPANYIE, Environmental Systems International, Vienna, Va. SHERYL BARTLETT, Health and Welfare Canada, Ottawa, Ontario JUDY HAUSWIRTH, Jellinek, Schwartz, Connolly and Freshman, Washington, D.C. JOHN P. WARGO, Yale University, New Haven, Conn. RICHARD WILES, Center for Resource Economics, Washington, D.C.
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Pesticides in the Diets of Infants and Children BOARD ON AGRICULTURE THEODORE L. HULLAR, Chair, University of California, Davis PHILIP H. ABELSON, American Association for the Advancement of Science, Washington, D.C. JOHN M. ANTLE, Montana State University, Bozeman DALE E. BAUMAN, Cornell University, Ithaca, N.Y. WILLIAM B. DeLAUDER, Delaware State College, Dover SUSAN K. HARLANDER, Land O'Lakes, Inc., Minneapolis, Minn. PAUL W. JOHNSON, Natural Resources Consultant, Decorah, Iowa T. KENT KIRK, U.S. Department of Agriculture, Forest Service, Madison, Wis. JAMES R. MOSELEY, Purdue University, West Lafayette, Ind. DONALD R. NIELSEN, University of California, Davis NORMAN R. SCOTT, Cornell University, Ithaca, N.Y. GEORGE E. SEIDEL, JR., Colorado State University, Fort Collins PATRICIA B. SWAN, Iowa State University, Ames JOHN R. WELSER, The Upjohn Company, Kalamazoo, Mich. FREDERIC WINTHROP, JR., The Trustees of Reservations, Beverly, Mass Staff SUSAN E. OFFUTT, Executive Director JAMES E. TAVARES, Associate Executive Director CARLA CARLSON, Director of Communications BARBARA J. RICE, Editor JANET OVERTON, Associate Editor
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Pesticides in the Diets of Infants and Children BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY PAUL G. RISSER, Chair, University of Miami, Oxford, Ohio FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, D.C. JOHN C. BAILAR III, McGill University School of Medicine, Montreal, Quebec, Canada GARRY D. BREWER, University of Michigan, Ann Arbor, Mich. JOHN CAIRNS, JR., Virginia Polytechnic Institute and State University, Blacksburg, Va. EDWIN H. CLARK, Department of Natural Resources and Environmental Control, State of Delaware, Dover, Del. JOHN L. EMMERSON, Lilly Research Laboratories, Greenfield, Ind. ROBERT C. FORNEY, Unionville, Pa. ALFRED G. KNUDSON, Fox Chase Cancer Center, Philadelphia, Pa. KAI LEE, Williams College, Williamstown, Mass. GENE E. LIKENS, The New York Botanical Garden, Millbrook, N.Y. JANE LUBCHENCO, Oregon State University, Corvallis, Oreg. DONALD MATTISON, University of Pittsburgh, Pittsburgh, Pa. HAROLD A. MOONEY, Stanford University, Stanford, Calif. GORDON ORIANS, University of Washington, Seattle, Wash. FRANK L. PARKER, Vanderbilt University, Nashville, Tenn., and Clemson University, Anderson, S.C. GEOFFREY PLACE, Hilton Head, S.C. MARGARET M. SEMINARIO, AFL/CIO, Washington, D.C. I. GLENN SIPES, University of Arizona, Tucson, Ariz. BAILUS WALKER, JR., University of Oklahoma, Oklahoma City, Okla. WALTER J. WEBER, JR., University of Michigan, Ann Arbor, Mich. Staff JAMES J. REISA, Director DAVID J. POLICANSKY, Associate Director and Program Director for Natural Resources and Applied Ecology RICHARD D. THOMAS, Associate Director and Program Director for Human Toxicology and Risk Assessment LEE R. PAULSON, Program Director for Information Systems and Statistics RAYMOND A. WASSEL, Program Director for Environmental Sciences and Engineering
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Pesticides in the Diets of Infants and Children COMMISSION ON LIFE SCIENCES THOMAS D. POLLARD, Chair, Johns Hopkins Medical School, Baltimore, Md. BRUCE N. AMES, University of California, Berkeley, Calif. J. MICHAEL BISHOP, Hooper Research Foundation, University of California Medical Center, San Francisco, Calif. DAVID BOTSTEIN, Stanford University School of Medicine, Stanford, Calif. MICHAEL T. CLEGG, University of California, Riverside, Calif. GLENN A. CROSBY, Washington State University, Pullman, Wash. LEROY E. HOOD, University of Washington, Seattle, Wash. MARIAN E. KOSHLAND, University of California, Berkeley, Calif. RICHARD E. LENSKI, University of Oxford, Oxford, United Kingdom STEVEN P. PAKES, Southwestern Medical Center, Dallas, Tex. EMIL A. PFITZER, Hoffmann-La Roche Inc., Nutley, N.J. MALCOLM C. PIKE, University of Southern California School of Medicine, Los Angeles, Calif. PAUL G. RISSER, Miami University, Oxford, Ohio JOHNATHAN M. SAMET, University of New Mexico School of Medicine, Albuquerque, N. Mex. HAROLD M. SCHMECK, JR., Armonk, N.Y. CARLA J. SHATZ, University of California, Berkeley, Calif. SUSAN S. TAYLOR, University of California at San Diego, La Jolla, Calif. P. ROY VAGELOS, Merck and Company, Inc., Whitehouse Station, N.J. TORSTEN N. WIESEL, Rockefeller University, New York, N.Y. Staff PAUL GILMAN, Executive Director
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Pesticides in the Diets of Infants and Children The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Frank Press is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Robert M. White is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Frank Press and Dr. Robert M. White are chairman and vice-chairman, respectively, of the National Research Council.
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Pesticides in the Diets of Infants and Children Preface IN 1988, THE U.S. CONGRESS requested that the National Academy of Sciences establish a committee within the National Research Council to study scientific and policy issues concerning pesticides in the diets of infants and children. The Committee on Pesticide Residues in the Diets of Infants and Children appointed to undertake this study was charged with responsibility for examining what is known about exposures to pesticide residues in the diets of infants and children, the adequacy of current risk assessment methods and policies, and toxicological issues of greatest concern. The committee operated under the joint aegis of the Board on Agriculture (BA) and the Board on Environmental Studies and Toxicology (BEST). The committee first met in October 1988 and held its last meeting in January 1993. Several full committee meetings were held each year, and subgroups of the committee were convened on a number of occasions to address such topics as the physiology of infants and children, the age-specific patterns of children's diets, the measurement of residue levels, and the mathematical modeling of risks. The expertise represented on the committee included pediatrics, toxicology, epidemiology, biostatistics, food science and nutrition, analytical chemistry, and child growth and development. When required, advice was obtained from experts outside the committee on a variety of topics. Critical assessment of potential risks to health resulting from exposures to toxicants in the environment has been the focus of several recent studies conducted by BEST and BA. Many of the approaches to risk assessment used in this report trace their origins to the reports on Drinking Water and
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Pesticides in the Diets of Infants and Children Health developed since 1977. Of particular value was Volume 6 in that series. The committee also found useful Risk Assessment in the Federal Government: Managing the Process (1983), Biologic Markers in Reproductive Toxicology (1989), Biologic Markers in Immunotoxicology (1992), and Environmental Neurotoxicology (1992). The analysis in this volume draws conceptually from the 1987 report from the Board on Agriculture called Regulating Pesticides in Food: The Delaney Paradox—an examination of the process by which levels of pesticide residues in foods are regulated by the U.S. Government. The Committee on Pesticides in the Diets of Infants and Children was greatly assisted by many individuals and groups who provided information on food consumption patterns and on pesticide residue concentrations in the U.S. diet. The groups include the U.S. Department of Agriculture, the U.S. Food and Drug Administration, the National Food Processors Association, the Gerber Products Company, and the Infant Formula Council. Many other food manufactures as well as pesticide manufacturers also provided useful data to the committee either individually or through various organizations. The committee is grateful for the assistance of the National Research Council (NRC) staff in the preparation of this report. In particular the committee wishes to acknowledge Frances Peter, project manager; Richard Thomas, principal staff scientist (BEST); Sandi Fitzpatrick, senior program assistant (BEST); James Reisa, director of BEST; and Susan Offutt, executive director of BA. Other staff members who contributed to this effort include Shelley A. Nurse, senior project assistant (BEST); Ruth P. Danoff, project assistant (BEST); Craig Cox, senior staff officer (BA); Mary Lou Sutton, administrative assistant (BA); Carla Carlson, director of communications (BA); Barbara J. Rice, editor (BA); Janet Overton, associate editor (BA); Lee. R. Paulson, program director for information systems and statistics (BEST); Bernidean Williams, information specialist (BEST); and Dawn M. Eichenlaub, production manager, and Richard E. Morris, editor, National Academy Press. Thanks are also due to Richard Wiles and Charles Benbrook, formerly of the BA staff. The interest in this report shown by the Executive Office of the National Research Council, especially by the Deputy Executive Officer Mitchel Wallerstein, is greatly appreciated. These individuals provided invaluable support to the committee throughout its deliberations. As consultant to the committee, John Wargo of the Yale University School of Forestry and Environmental Studies developed numerous innovative approaches to the analysis of highly complex data. His pellucid presentations permitted clear understanding of issues that previously had been opaque. Valuable assistance was also provided to the committee by Emmanuel Akpanyie, Sheryl Bartlett, and Judy Hauswirth, who served as technical advisers, and Dr. Marcia VanGemert, the EPA project officer.
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Pesticides in the Diets of Infants and Children Last, but by no means least, the work of all the members of the committee is greatly appreciated. We are also grateful to the U. S. Environmental Protection Agency, Health and Welfare Canada, the International Life Sciences Institute, and the Kellogg Endowment Fund of the National Academy of Sciences and the Institute of Medicine, whose financial support made the study possible. PHILIP J. LANDRIGAN, M.D., M.Sc. Chairman
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Pesticides in the Diets of Infants and Children This page in the original is blank.
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Pesticides in the Diets of Infants and Children Contents EXECUTIVE SUMMARY 1 1 BACKGROUND AND APPROACH TO THE STUDY 13 Pesticide Use 14 Pesticide Control Legislation 17 Approach to the Study 18 References 22 2 SPECIAL CHARACTERISTICS OF CHILDREN 23 Growth 25 Development 36 Conclusions and Recommendations 42 References 44 3 PERINATAL AND PEDIATRIC TOXICITY 49 Acute Toxicity 49 Neurotoxicity 60 Immunotoxicity 66 Carcinogenesis and Mutagenesis 70 Metabolism and Pharmacokinetics 76
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Pesticides in the Diets of Infants and Children Scaling and Progression Analysis 96 Conclusions and Recommendations 105 References 110 4 METHODS FOR TOXICITY TESTING 127 Current Methods: General Considerations 128 Acute Toxicity Studies 133 Subchronic Toxicity Studies 137 Chronic Toxicity Studies 145 Developmental Toxicity Studies 146 Reproduction Studies 147 Mutagenicity Studies 150 General Metabolism Studies 150 Neurotoxicity Studies 151 Special Testing 152 Conclusions and Recommendations 152 References 156 5 FOOD AND WATER CONSUMPTION 159 Food Consumption Surveys 159 Survey Methodology 161 Survey Design 164 Sample Weights 167 Sample Size 167 Comparisons of Intake Data with Standards 167 Validation of Food Consumption Data 168 The Strengths and Weaknesses of the Food Consumption Data Bases in Estimating Pesticide Exposure of Children 169 Water Intake 172 Quantification of Consumption Data 177 Age-Related Differences in Dietary Patterns 181 Issues Related to the Evaluation of Food Monitoring Data 194 Conclusions and Recommendations 195 References 197 6 PESTICIDE RESIDUES 203 Sources of Data on Usage 203
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Pesticides in the Diets of Infants and Children The Occurrence and Fate of Pesticide Residues 206 Pesticide Registration and the Development of Analytical Methods 207 Methods for Sampling and Analysis 210 Monitoring 215 Quality Controls 223 Limitations of the Data 224 Pesticides in Water 227 Pesticides in Infant Formula 232 Pesticides in Human Milk 239 Pesticides in Foods 244 Conclusions and Recommendations 260 References 263 7 ESTIMATING EXPOSURES 267 The Use of Food Consumption and Residue Data for Exposure Assessment 270 Long-Term Exposure to Benomyl 277 Short-Term Exposure to Aldicarb 287 Multiple Exposure Assessment: Organophosphate Insecticides 297 Nondietary Exposure to Pesticides 307 Conclusions and Recommendations 314 References 319 8 ESTIMATING THE RISKS 323 General Principles of Risk Assessment 324 Risk Assessments for Infants and Children 339 Conclusions and Recommendations 359 References 363 INDEX 373